Study of the Efficacy, Safety and Pharmacokinetics of Pamiparib (BGB-290) in Participants With Advanced Solid Tumors

BeiGene128 enrolled

Overview

This study is designed to evaluate the safety, tolerability, PKharmacokinetic profile and treatment effect of pamiparib in Chinese participants with advanced high-grade ovarian cancer (including fallopian cancer or primary peritoneal cancer) and triple negative breast cancer in phase I, and to evaluate the efficacy and safety of pamiparib in Chinese participants with recurrent epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline breast cancer susceptibility gene 1/gene 2 (BRCA1/2) mutation in phase II.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

128

Conditions

Advanced High-grade Ovarian Cancer Triple Negative Breast Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Participants have voluntarily agreed to participate by giving written informed consent. 2. Age 18 years (including 18 years) on the day of signing informed consent. 3. Participants meet the following eligibility criteria for the corresponding part of the study: 1) In Phase 1 portion: The participants must have a histologically or cytologically confirmed locally advanced or metastatic cancer, either triple-negative breast cancer or epithelial, non-mucinous, high-grade ovarian cancer (including fallopian cancer, or primary peritoneal cancer), for which no effective standard therapy is available. 2\) In Phase 2 portion: Participants who have histologically or cytologically confirmed high-grade epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline BRCA1/2 mutation 4. Participants must have measurable disease as defined per the RECIST, version 1.1. 5\. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Key Exclusion Criteria: 1. Participants who have been treated with chemotherapy, biologic therapy, immunotherapy, investigational agent, anti-cancer Chinese medicine, or anticancer herbal remedies ≤ 14 days (or ≤5 half-lives, whichever is shorter) prior to starting study drug, or who have not adequately recovered from the side effects of such therapy. 2. Participants who have undergone major surgery for any cause ≤ 4 weeks prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. 3. Participants who have undergone radiotherapy for any cause ≤ 14 days prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. 4. Untreated and/or active brain metastases. 5. Prior therapies targeting poly (ADP-ribose) polymerase (PARP). NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (6)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Outcomes

Primary Outcomes

Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)

Time frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)

Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs)

Time frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)

Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC)

ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response

Time frame: Up to approximately 2 years and 8 months

Secondary Outcomes

Phase I: Maximum Observed Plasma Concentration (Cmax)

Time frame: Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase I: Time to Reach Cmax (Tmax)

Time frame: Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase I: Terminal Elimination Half-life (t1/2)

Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase I: Apparent Clearance (CL/F)

Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)

Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F)

Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose

Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1

ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR)

Time frame: Up to approximately 36 months

Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1

DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)

Time frame: Up to approximately 36 months

Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1

CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks

Time frame: Up to approximately 36 months

Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1

DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first

Time frame: Up to approximately 36 months

Phase I : Progression Free Survival (PFS)

PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first

Time frame: Up to approximately 36 months

Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1

ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response